Acetate-induced depression of electrical and contractile activity in normoxic and hypoxic guinea pig papillary muscle

Abstract

The action potential configuration, developed tension, and resting tension were monitored in normoxic and hypoxic guinea pig papillary muscles superfused with solutions containing no substrate, glucose, or acetate (1–10 mM). In normoxic muscle, acetate provoked a concentration-dependent transient depression of the action potential duration and force of contraction, depression was maximal after 10–30 min, and recovery was complete after 90–120 min. In hypoxic muscle, acetate accelerated functional rundown (action potential shortening, decline of developed tension, increase in resting tension). Because rundown in hypoxic muscle was sensitive to factors affecting glycolysis (moderated by external glucose; accentuated by 2-deoxyglucose), the accentuated rundown with acetate may be accounted for by a partial block of glycolysis. However, block of glycolysis cannot explain the acetate-induced transient depression in normoxic muscle, since the depression was enhanced in normoxic muscle with 2-deoxyglucose-blocked glycolysis. We suggest that the transient depression is due to a transient depression of high energy nucleotides with consequent effects on ionic currents.Key words: acetate, action potential duration, 2-deoxyglucose, hypoxia, ATP.